skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Aging phenotypes in cultured normal human mammary epithelial cells are correlated with decreased telomerase activity independent of telomere length

Journal Article · · Genome Integrity
 [1];  [1];  [1];  [1];  [1];  [1]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Science Division
+ Show Author Affiliations

Shortening of telomeres, which are essential for maintenance of genomic integrity, is a mechanism commonly associated with the aging process. Here we ascertained whether changes in telomere lengths or telomerase activity correlated with age in normal human mammary epithelial cells (HMEC), or with phenotypes of aging in breast. Accordingly, flow cytometry fluorescence in situ hybridization (flowFISH) was used to determine relative telomere lengths (RTL), and telomerase activity was measured by the telomeric repeat amplification protocol (TRAP), in a collection of 41 primary HMEC strains established from women aged 16 to 91 years. RTL measurements of HMEC strains that were heterogeneous with respect to lineage composition revealed no significant associations between telomere length with age, maximum observed population doublings, or with lineage composition of the strains. However, within strains, luminal epithelial and cKit-expressing epithelial progenitor cells that were flow cytometry-enriched from individual HMEC strains exhibited significantly shorter telomeres relative to isogenic myoepithelial cells (P < 0.01). In unsorted strains, detectable telomerase activity did not correlate with RTL. Telomerase activity declined with age; the average age of strains that exhibited TRAP activity was 29.7 ± 3.9y, whereas the average age of strains with no detectable TRAP activity was 49.0 ± 4.9y (P < 0.01). Non-detectable TRAP activity also was correlated with phenotypes of aging previously described in HMEC strains; increased proportions of CD227-expressing luminal epithelial cells (P < 0.05) and cKit-expressing progenitor cells (P < 0.05). Telomere shortening did not correlate with the chronological ages of HMEC strains, whereas decreased telomerase activity correlated with age and with lineage distribution phenotypes characteristic of aging.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1629602
Journal Information:
Genome Integrity, Vol. 4, Issue 1; ISSN 2041-9414
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

References (35)

Analyses and comparisons of telomerase activity and telomere length in human T and B cells: Insights for epidemiology of telomere maintenance journal January 2010
Luminal and cancer cells in the breast show more rapid telomere shortening than myoepithelial cells and fibroblasts journal November 2008
Gradual Phenotypic Conversion Associated with Immortalization of Cultured Human Mammary Epithelial Cells journal December 1997
Telomere Shortening in Kidneys with Age journal March 2000
Telomere Shortening Occurs in Subsets of Normal Breast Epithelium as well as in Situ and Invasive Carcinoma journal March 2004
Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and is overcome in immortal cells during conversion journal September 2002
Telomerase Activity in Normal Ovaries and Premature Ovarian Failure journal January 2000
GATA-3 Links Tumor Differentiation and Dissemination in a Luminal Breast Cancer Model journal February 2008
Telomere analysis by fluorescence in situ hybridization and flow cytometry journal August 1998
Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition journal January 2002
BRCA1 Basal-like Breast Cancers Originate from Luminal Epithelial Progenitors and Not from Basal Stem Cells journal September 2010
Expression of the telomerase catalytic subunit, hTERT, induces resistance to transforming growth factor β growth inhibition in p16INK4A(−) human mammary epithelial cells journal April 2001
Telomeres shorten during ageing of human fibroblasts journal May 1990
Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. journal October 1994
Actions of human telomerase beyond telomeres journal June 2008
Regulation of In Situ to Invasive Breast Carcinoma Transition journal May 2008
Telomere lengths are characteristic in each human individual journal April 2002
Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals journal April 1998
Basal cells have longest telomeres measured by tissue Q-FISH method in lingual epithelium journal September 2008
Accelerated telomere shortening in response to life stress journal December 2004
Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate journal February 2011
Processing of Human Reduction Mammoplasty and Mastectomy Tissues for Cell Culture journal January 2013
Separation of telomerase functions by reverse genetics journal September 2011
Telomere Fluorescence Measurements in Granulocytes and T Lymphocyte Subsets Point to a High Turnover of Hematopoietic Stem Cells and Memory T Cells in Early Childhood journal July 1999
Molecular Distinctions between Stasis and Telomere Attrition Senescence Barriers Shown by Long-term Culture of Normal Human Mammary Epithelial Cells journal September 2009
Accumulation of Multipotent Progenitors with a Basal Differentiation Bias during Aging of Human Mammary Epithelia journal May 2012
Oncogenes induce senescence with incomplete growth arrest and suppress the DNA damage response in immortalized cells: Oncogenes induce atypical senescence phenotype journal September 2011
Lineage-Specific Telomere Shortening and Unaltered Capacity for Telomerase Expression in Human T and B Lymphocytes with Age journal August 2000
The role of insulin and IGF-1 signaling in longevity journal February 2005
The rate of telomere sequence loss in human leukocytes varies with age journal May 1998
Telomere length variations in 6 mucosal cell types of gastric tissue observed using a novel quantitative fluorescence in situ hybridization method journal August 2007
Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers journal August 2009
Comparative transcriptional analyses of preclinical models and patient samples reveal MYC and RELA driven expression patterns that define the molecular landscape of IBC journal January 2022
Growth of normal human mammary cells in culture journal May 1980
A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan journal June 2002

Cited By (3)

Cell Fate Decisions During Breast Cancer Development journal January 2016
The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas journal October 2013
Current relevance of hypoxia in head and neck cancer journal May 2016

Similar Records

Investigating YAP’s role in Human Mammary Epithelial Cell (HMEC) Immortalization and Cancer Stem Cell (CSC) Phenotype Acquisition during Early Breast Cancer Progression
Conference · Wed Aug 07 00:00:00 EDT 2019 · OSTI ID:1629602
+1 more
p57KIP2 expression and loss of heterozygosity during immortal conversion of cultured human mammary epithelial cells
Journal Article · Sun Aug 01 00:00:00 EDT 1999 · Cancer Research · OSTI ID:1629602
+3 more
Different culture media modulate growth, heterogeneity, and senescence in human mammary epithelial cell cultures
Journal Article · Mon Oct 01 00:00:00 EDT 2018 · PLoS ONE · OSTI ID:1629602
+3 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Aging
Human mammary epithelial cell
HMEC
Telomere
Telomerase